The purpose of this grant is to complete a case-control study of DNA polymorphisms and head and neck cancer risks. It has been appreciated for sometime that genes play a critical role in the risk for cancer development. The familial cancer syndromes such as Li- Fraumeni syndrome and xeroderma pigmentosa are dramatic examples of the way genetic changes can affect cancer rise However, it is also appreciated that different allelic forms of genes (polymorphisms) may also affect an individual's cancer risk, particularly when these polymorphisms exist in genes which metabolize xenobiotics, are involved in DNA repair/replication, or are tumor suppressor genes. Polymorphisms have been identified which occur frequently that moderately increase a person's risk for developing cancer. Because the polymorphism occurs frequently, it is responsible for a significant proportion of the cancers in the population in contrast to the rare familial syndromes, which have little bearing on the incidence of cancer in the general population. This proposal plans to examine the effect of certain gene polymorphisms on the risk of developing head and neck squamous cell carcinoma. Specifically, polymorphisms of the GSTM1, CYP1A1, CYP2D6, CYP2E1, NA72, and P53 genes will be studied in a case-control fashion using PCR and restriction fragment length polymorphisms techniques. Statistical methods will be used to decrease potential biases and multi-variate analyses will be used to assess possible interactions among polymorphisms. The results of this proposed study will be used to develop further studies examining the association between genetic polymorphisms and cancer, including studies concerning the risk of developing other malignancies, such as breast cancer, as well as studies of risks of tumor recurrence, response to therapy, and risks of second malignancies.